Details of Disease

General Information of Disease (ID: DISO1UQ2)

• Disease Name: Congenital hypothalamic hamartoma syndrome
• Synonyms: hamartoma of the hypothalamus; congenital hypothalamic hamartoma syndrome; hamartoma of hypothalamus; hypothalamic hamartomas; Pallister-Hall-like syndrome; hypothalamic hamartoma
• Definition: Hypothalamic hamartomas (HH) are rare, tumor-like malformations that occur during fetal development and are present at birth. The lesions usually do not change in size or spread to other locations. Both the type and severity of symptoms vary greatly among patients with hypothalamic hamartomas. Common symptoms include frequent gelastic seizures (spontaneous laughing, giggling and/or smirking) or dacrystic seizures (crying or grunting); developmental delays; and/or precocious puberty. Additional symptoms may include cognitive impairment; emotional and behavioral difficulties; and endocrine disturbances. These symptoms often start early in life but are frequently misdiagnosed. For some patients, endocrine (hormonal) disturbances such as central precocious puberty may be the only symptom. These patients can often be treated successfully with medications. For some, however, HH can be disabling. For those with HH and epilepsy, it is common for the disorder to progress and for different types of seizures to develop. The seizures associated with HH often cannot be well-controlled with the standard seizure medications. For some, additional treatment such as surgical removal, radiosurgery, or thermoablation may be indicated. Though hypothalamic hamartomas can occur in patients with certain genetic disorders (such as Pallister-Hall syndrome), the majority of cases are sporadic.
• Disease Hierarchy:
  DISTYTPU: Pallister-Hall syndrome
  DISO1UQ2: Congenital hypothalamic hamartoma syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0009436
  MESH ID: C537158
  UMLS CUI: C0342418
  MedGen ID: 137970
  HPO ID: HP:0002444
  Orphanet ID: 2113
  SNOMED CT ID: 237714006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SMO	TTW6JVU	Moderate	Autosomal recessive	[1]
SOX2	TTCNOT6	moderate	Biomarker	[2]
GJD2	TTOZAFI	Strong	Altered Expression	[3]
PRKACA	TT5U49F	Strong	Genetic Variation	[4]
SLC12A5	TTH6UZY	Strong	Altered Expression	[5]
SLC25A4	TTU5A6Q	Strong	Altered Expression	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A6	DTLMGFJ	Strong	Altered Expression	[6]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SMO	OTXXE208	Moderate	Autosomal recessive	[1]
GLI3	OTKDOE94	Strong	Genetic Variation	[7]
POU3F4	OTKF5AF7	Strong	Biomarker	[8]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma. Am J Med Genet A. 2018 Dec;176(12):2710-2719. doi: 10.1002/ajmg.a.40644. Epub 2018 Nov 18.
• [3] Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas.EBioMedicine. 2016 Jun;8:96-102. doi: 10.1016/j.ebiom.2016.04.026. Epub 2016 Apr 22.
• [4] Mutations of the Sonic Hedgehog Pathway Underlie Hypothalamic Hamartoma with Gelastic Epilepsy.Am J Hum Genet. 2016 Aug 4;99(2):423-9. doi: 10.1016/j.ajhg.2016.05.031. Epub 2016 Jul 21.
• [5] Hyperactivation of BDNF-TrkB signaling cascades in human hypothalamic hamartoma (HH): a potential mechanism contributing to epileptogenesis.CNS Neurosci Ther. 2015 Feb;21(2):164-72. doi: 10.1111/cns.12331. Epub 2014 Oct 13.
• [6] Recent advances in the neurosurgical treatment of pediatric epilepsy: JNSPG 75th Anniversary Invited Review Article.J Neurosurg Pediatr. 2019 Apr 5;23(4):411-421. doi: 10.3171/2018.12.PEDS18350.
• [7] Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.Pediatr Dev Pathol. 2018 May-Jun;21(3):324-331. doi: 10.1177/1093526617701338. Epub 2017 Apr 21.
• [8] Hypothalamic hamartomas and inner ear diverticula with X-linked stapes gusher syndrome - new associations?.Pediatr Radiol. 2020 Jan;50(1):142-145. doi: 10.1007/s00247-019-04497-z. Epub 2019 Aug 22.